We propose to carry out investigations of threshold conditions for changes in biological systems produced by ultrasound. Experimental work on selected cellular, intracellular and macromolecular systems will be carried out in collaboration between physically and biologically trained scientists. Much emphasis will be placed on design of experiments according to available knowledge, and analysis of results to determine basic principles involved. Physical theory will be developed where required, and experiments on model systems carried out to test hypotheses. The broad aim is to develop methods for calculating dose parameters (frequency, amplitude-distribution or intensity-distribution, pulse regime, time of irradiation, etc.) of an ultrasonic field which lead to specified changes in given biological systems. Such methods and information is of critical significance in the rapidly growing field of medical ultrasonics. We expect our work to be part of a wide-ranging effort to determine the safety of diagnostic procedures and the efficacy of therapeutic treatment with ultrasound involving investigators at a number of institutions. Our biophysical approach, using relatively simple biological units and models is meant to complement other work with more complex systems, by providing basic insights into the etiology of biological effects of ultrasound.